Facts About Biosimilars
Full update September 2021
Numerous biosimilars are available in the
U.S., and the list is growing. The differences
between biosimilars, biologics, interchangeable products, and generics, as well
as their various approval processes can be confusing. Biosimilars may be preferred by payers as
they are less costly than the reference product (but still expensive). The FAQ below addresses questions that may
come up regarding biosimilars, including interchangeability.
are biological products and biosimilars?
Biological products are generally isolated from living
material (human, animal, or microorganism) and may be produced by
biotechnology methods or other technologies.2 They are much larger and more
complex molecules or mixture of molecules than a traditional drug.9
Biosimilars are biological products that have been
shown to be highly similar to an FDA-approved
biological product (known as the reference
do biosimilars receive FDA approval?
Biosimilars are approved through an abbreviated pathway
created via the Biologics Price Competition and Innovation Act, that relies
on existing safety and efficacy data of the reference product.1,12
A biosimilar product
can only be approved by the FDA:
The manufacturer’s application for a
biosimilar must include, among other things, information demonstrating biosimilarity based upon data from:1
There are additional requirements for interchangeable biologics, described later in this document.
more than one biologic with the same active ingredient be approved via the
new drug pathway?
Multiple biologics with the same active ingredient can each be approved as new drugs (not as biosimilars), for example:
does a biosimilar differ from a generic?
Biosimilars are not generics. Biosimilars and generics are approved
through different abbreviated pathways.2
Generic drugs are almost identical to the brand
name drug. Small-molecule
(“traditional”) drugs are made through a predictable set of chemical
reactions. However, biologics are made
using manufacturing processes (e.g., cell production, purification processes)
and living organisms (e.g., cell lines) that are unique to each manufacturer,
making it impossible to make an exact copy of a biologic.11
FDA-approved generic drugs must contain the same active ingredient(s) as the brand-name/innovator drug (inactive ingredients may vary), be identical in strength, dosage form, and route of administration, have the same indications, and be bioequivalent (i.e., work in the same way and provide the same clinical benefit).6
In some cases, biologics may be approved through the generic drug approval pathway.
biosimilars interchangeable with the reference product?
Biosimilars do not fall under the same
rules for generic substitution as traditional drugs.
biologic is biosimilar to an FDA-approved reference product and meets
additional standards for interchangeability.1 Therefore, not all biosimilars are
interchangeable. (See next section for
info on identifying interchangeable biologics.)
Federal regulations allow an interchangeable biologic to be
substituted for the reference product by a pharmacist without the
intervention of the prescriber.5 However, state pharmacy boards
may have different regulations.8,18
To be interchangeable, an
FDA-approved biosimilar must also prove that:1
do you find out if a biosimilar and reference product are interchangeable?
The Purple Book
Biosimilar and interchangeable biologics licensed under section 351(k) of the Public Health Service Act are listed under the reference product to which biosimilarity or interchangeability was demonstrated.4
are biosimilars named?
The FDA’s naming convention for all biological
products is a “core name” followed by an FDA-designated suffix composed of
four lowercase letters attached to the core name with a hyphen.3 Most
of the suffixes are nonsensical.3
The suffix format applies to originator
biological products as well as biosimilars.
Products without suffixes, or with suffixes that do not comply with
the guidance, will receive new suffixes over time. The FDA is continuing to consider the
appropriate suffix format for interchangeable products.3
are some practical prescribing and dispensing implications for biosimilars?
A biosimilar can be approved only for those
indications previously approved for the reference product, but a biosimilar
can be approved for fewer than all
the indications and routes approved for the reference product.13,14 This could happen if the reference product has
an unexpired patent(s) on an indication, the biosimilar manufacturer only
applies for certain indications, or the FDA does not allow the indication
after reviewing the submitted data.1,16
Interchangeable biosimilars may be substituted by the pharmacist without the
intervention of the prescriber (depending on state law).8,18 (This is analogous to substitution by the
pharmacist of an A-rated generic.)
For noninterchangeable products, prescribers
should specify the biosimilar’s unique name to ensure the desired product is
dispensed. For example, if Zarxio is
desired, write the brand name or specific nonproprietary name (e.g.,
filgrastim-sndz) instead of just “filgrastim.” Be aware that in the hospital setting, a
formulary-directed substitution might be made.
Pharmacists should be aware of state laws on dispensing
biosimilars. Some states may require the prescriber and/or patient to be
notified if a substitution is made at the pharmacy.15,18 Details of individual state regulations around biosimilar interchangeability can be
found at https://www.cardinalhealth.com/content/dam/corp/web/documents/publication/Cardinal-Health-Biosimilar-Interchangeability-Laws-by-State.pdf.
patients stick with the same biologic?
biological product can be expected to produce the same clinical result
as the reference product in any given patient.5,8,16
biological products must show that (for products administered more than once
to an individual) the risk in regard to safety or diminished efficacy of
alternating or switching between use of the biological product and the
reference product is not greater than the risk of using the reference product
without such alternation or switch.1
- FDA. Biosimilar development, review, and approval. Page current as of October 20, 2017. https://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/Biosimilars/ucm580429.htm. (Accessed August 15, 2021).
- FDA. Biological product definitions. https://www.fda.gov/files/drugs/published/Biological-Product-Definitions.pdf. (Accessed August 16, 2021).
- FDA. Nonproprietary naming of biological products. Guidance for industry. Page current as of November 18, 2019. https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM459987.pdf. (Accessed August 15, 2021).
- Food and Drug Administration. Purple Book: lists of licensed biological products with reference product exclusivity and biosimilarity or interchangeability evaluations. Page current as of August 3, 2020. http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/Biosimilars/ucm411418.htm. (Accessed August 15, 2021).
- FDA. Biosimilar and interchangeable products. Page current as of October 23, 2017. https://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/Biosimilars/ucm580419.htm#biological. (Accessed August 15, 2021).
- FDA. Generic drugs: questions and answers. Content current as of March 16, 2021. http://www.fda.gov/Drugs/ResourcesForYou/Consumers/QuestionsAnswers/ucm100100.htm. (Accessed August 15, 2021).
- FDA. Information for patients about regulatory changes for certain biological product medications. March 23. 2020. https://www.fda.gov/media/135341/download. (Accessed August 16, 2021).
- FDA. Prescribing interchangeable biologics. https://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/Biosimilars/UCM581343.pdf. (Accessed August 15, 2021).
- Lucio SD, Stevenson JG, Hoffman JM. Biosimilars: primer for the health-system pharmacist. Am J Health Syst Pharm 2013;70:2004-14.
- Drugs@FDA. FDA approved drug products. http://www.accessdata.fda.gov/Scripts/cder/DrugsatFDA/index.cfm. (Accessed August 15, 2021).
- Camacho LH, Frost CP, Abella E, et al. Biosimilars 101: considerations for U.S. oncologists in clinical practice. Cancer Med 2014;3:889-99.
- FDA. Implementation of the biologics price competition and innovation act of 2009. Page current as of February 12, 2016. https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/ucm215089.htm. (Accessed August 15, 2021).
- Lim S. Overview of the regulatory framework and FDA’s guidance for the development and approval of biosimilar and interchangeable product in the U.S. https://www.fda.gov/media/113820/download. (Accessed August 16, 2021).
- FDA. Labeling for biosimilar products. Guidance for industry. Page current as of November 18, 2019. https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM493439.pdf. (Accessed August 15, 2021).
- Cauchi R. State laws and legislation related to biologic medications and substitution of biosimilars. May 3, 2019. http://www.ncsl.org/research/health/state-laws-and-legislation-related-to-biologic-medications-and-substitution-of-biosimilars.aspx. (Accessed August 15, 2021).
- FDA. Prescribing biosimilar and interchangeable products. Page current as of October 23, 2017. https://www.fda.gov/drugs/biosimilars/prescribing-biosimilar-and-interchangeable-products. (Accessed August 15, 2021).
- FDA. Developing the tools to evaluate complex drug products: peptides. Content current as of February 5, 2019. https://www.fda.gov/Drugs/ScienceResearch/ucm578111.htm. (Accessed August 15, 2021).
- Cardinal Health. Biosimilar interchangeability laws by state. July 2021. https://www.cardinalhealth.com/content/dam/corp/web/documents/publication/Cardinal-Health-Biosimilar-Interchangeability-Laws-by-State.pdf. (Accessed August 16, 2021).
this document as follows: Clinical Resource,
Facts About Biosimilars. Pharmacist’s
Letter/Prescriber’s Letter. September